Until recently, arteriosclerosis (ATS) and inflammation were thought of as opposite biological events: one "passive and degenerative", the other "active and reparative". It is now clear that the two have much in common: the beginning of ATS have the appearance of a low-grade inflammation (a fortunate development, because the inflammatory process is relatively well understood). The purpose of this project is to investigate several aspects of ATS that are related to inflammation. We will use a relatively inexpensive animal model (rats fed supplements of cholesterol), and we will compare the results with lesions found in human arteries obtained by surgery. (a) THE STICKING OF CELLS TO THE VASCULAR WALL, a main characteristic of inflammation, is also characteristic of early ATS. Could it be that the major risk factors of ATS (hypertension, smoking, diabetes) operate by enhancing the cellular sticking? This question should be easily answered using our rat model of ATS. (b) THE REGRESSION of arteriosclerosis is now known to be a possibility. Does it correspond to a decrease in the "cellular sticking" just described? (c) WHAT TYPES OF WHITE BLOOD CELLS ARE INVOLVED IN ARTERIOSCLEROSIS? It is important to answer this question because we found that a significant proportion of the cells involved (in human and animal ATS) are LYMPHOCYTES, cells with many capabilities, which may play a key role in the development of the lesions. (d) Past studies on experimental ATS have found that three sets of events can occur: CELL STICKING, INCREASED PERMEABILITY (also typical of inflammation) and DEPOSITION OF FAT. How do these three events correlate in time and in space? Which one comes first? Does any one bring about the other two? (e) HOW DOES ATS RELATED TO "ALLERGY"? It has long been thought that there may be a relationship between the two. We plan to induce (in a major artery of the rat) the variety of allergy known as DELAYED HYPERSENSITIVITY: in essence, a form of poison ivy. Then we will see how the resulting lesion relates to that of ATS. (f) WHAT KIND OF CELLULAR RESPONSES ARE INDUCED BY CHOLESTEROL COMPOUNDS, if they are introduced under the skin? The answers may well help understand some of the arterial changes induced by these compounds. (g) THE TYPICAL LESION OF ATS INCLUDES A CENTRAL CORE OF DEAD TISSUE ("atheroma"). Its genesis is not understood. We have a working hypothesis to explain how it develops; we hope to find the answer by injecting a cholesterol compound into the skin and studying the cellular reaction to it.